Background: Depression and sexual problems are common in patients with coronary artery disease (CAD) and can influence their quality of life. Objectives: The aim of this study was to compare the efficacy of saffron and its main constituent, crocin, in improving mental and sexual health and ultimately quality of life in CAD patients. Methods: This double-blind, placebo-controlled, randomized clinical trial was carried out during 8 weeks in 3 groups, including 1 placebo and 2 intervention groups. The study sample included 58 CAD patients within the age range of 40 -65 years, referred to Shahid Madani cardiovascular hospital, Tabriz, Iran, from April 2015 to November 2016. The intervention groups received saffron aqueous extract (SAE; 30 mg; n, 20) or crocin (30 mg; n,19). All the groups completed the demographic questionnaire, Beck depression inventory-II (BDI-II), Hulbert index of sexual desire (HISD), and MacNew health-related quality of life questionnaire.